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Breast cancer immunotherapy

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https://www.readbyqxmd.com/read/28537911/a-novel-immunotherapy-targeting-mmp-14-limits-hypoxia-immune-suppression-and-metastasis-in-triple-negative-breast-cancer-models
#1
Binbing Ling, Kathleen Watt, Sunandan Banerjee, Daniel Newsted, Peter Truesdell, Jarrett Adams, Sachdev S Sidhu, Andrew Wb Craig
Matrix metalloproteinase-14 (MMP-14) is a clinically relevant target in metastatic cancers due to its role in tumor progression and metastasis. Since active MMP-14 is localized on the cell surface, it is amenable to antibody-mediated blockade in cancer, and here we describe our efforts to develop novel inhibitory anti-MMP-14 antibodies. A phage-displayed synthetic humanized Fab library was screened against the extracellular domain of MMP-14 and a panel of MMP14-specific Fabs were identified. A lead antibody that inhibits the catalytic domain of MMP-14 (Fab 3369) was identified and treatment of MDA-MB-231 breast cancer cells with Fab 3369 led to significant loss of extracellular matrix degradation and cell invasion abilities...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537889/immune-signature-of-metastatic-breast-cancer-identifying-predictive-markers-of-immunotherapy-response
#2
Ji-Yeon Kim, Eunjin Lee, Kyunghee Park, Woong-Yang Park, Hae Hyun Jung, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
In breast cancer (BC), up to 10-20% patients were known to have clinical benefit with immune checkpoint inhibitors, and biomarkers are needed for optimal use of this multi-potential therapeutic strategy. Accordingly, we conducted an experiment to identify expression of genes associated with immune checkpoints that represent potential targets of cancer immunotherapy. We performed whole-transcriptome sequencing and whole-exome sequencing using 37 refractory BC specimens. In the immune pathway gene set expression analysis, we found that HER2 expression and previous taxane treatment were positively correlated with high expression of immune gene set expression (p = 0...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28534250/advancing-immunotherapy-in-metastatic-breast-cancer
#3
REVIEW
Mariam Mansour, Zhi Ling Teo, Stephen J Luen, Sherene Loi
Despite many advances in the treatment of breast cancer, the development of metastatic disease remains an incurable and frequent cause of cancer death for women worldwide. An improved understanding of the role of host immunosurveillance in modulating breast cancer disease biology, as well as impressive survival benefits seen to checkpoint blockade in other malignancies have provided great hope for an expanding role of immunotherapies in breast cancer management. While these novel therapies are currently being investigated in clinical trials, signals of efficacy, and tolerability in early phase studies suggest these will eventually make their way into standard practice algorithms...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28533483/high-il-1r8-expression-in-breast-tumors-promotes-tumor-growth-and-contributes-to-impaired-antitumor-immunity
#4
Luis Felipe Campesato, Ana Paula M Silva, Luna Cordeiro, Bruna R Correa, Fabio C P Navarro, Rafael F Zanin, Marina Marçola, Lilian T Inoue, Mariana L Duarte, Martina Molgora, Fabio Pasqualini, Matteo Massara, Pedro Galante, Romualdo Barroso-Sousa, Nadia Polentarutti, Federica Riva, Erico T Costa, Alberto Mantovani, Cecilia Garlanda, Anamaria A Camargo
Tumors develop numerous strategies to fine-tune inflammation and avoid detection and eradication by the immune system. The identification of mechanisms leading to local immune dysregulation is critical to improve cancer therapy. We here demonstrate that Interleukin-1 receptor 8 (IL-1R8 - previously known as SIGIRR/TIR8), a negative regulator of Toll-Like and Interleukin-1 Receptor family signaling, is up-regulated during breast epithelial cell transformation and in primary breast tumors. IL-1R8 expression in transformed breast epithelial cells reduced IL-1-dependent NF-κB activation and production of pro-inflammatory cytokines, inhibited NK cell activation and favored M2-like macrophage polarization...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28529637/role-of-the-cxcl8-cxcr1-2-axis-in-cancer-and-inflammatory-diseases
#5
REVIEW
Helen Ha, Bikash Debnath, Nouri Neamati
The chemokine receptors CXCR1/2 and their ligand CXCL8 are essential for the activation and trafficking of inflammatory mediators as well as tumor progression and metastasis. The CXCL8-CXCR1/2 signaling axis is involved in the pathogenesis of several diseases including chronic obstructive pulmonary diseases (COPD), asthma, cystic fibrosis and cancer. Interaction between CXCL8 secreted by select cancer cells and CXCR1/2 in the tumor microenvironment is critical for cancer progression and metastasis. The CXCL8-CXCR1/2 axis may play an important role in tumor progression and metastasis by regulating cancer stem cell (CSC) proliferation and self-renewal...
2017: Theranostics
https://www.readbyqxmd.com/read/28514195/analysis-of-the-use-and-impact-of-twitter-during-american-society-of-clinical-oncology-annual-meetings-from-2011-to-2016-focus-on-advanced-metrics-and-user-trends
#6
Naveen Pemmaraju, Michael A Thompson, Ruben A Mesa, Tejas Desai
PURPOSE: The use of social media, in particular Twitter, has substantially increased among health care stakeholders in the field of hematology and oncology, with an especially sharp increase in the use of Twitter during times of major national meetings. The most attended meeting in the oncology field is the ASCO annual meeting. Little is known about the detailed metrics involved in the use, volume, and impact of Twitter during the ASCO annual meeting. METHODS: We conducted a retrospective review of tweets during the ASCO annual meetings from 2011 to 2016...
May 17, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28509606/combined-immunotherapy-of-breast-cancer-with-egf-and-vegf-vaccines-from-dna-shuffling-in-a-mouse-model
#7
Dong Jin, Xin Yu, Bing Chen, Zhitao Li, Jia Ding, Xiuyun Zhao, Gaofu Qi
AIM: Development of EGF and VEGF vaccines with high antigenicity for combined immunotherapy of EGF-EGFR signaling-dependent epithelial tumors such as breast cancer. METHOD:  EGF genes from mouse, human and chicken were randomly assembled to chimeric genes by DNA shuffling, then a chimeric EGF was selected out by PCR, SDS-PAGE and immunization for combined immunotherapy of breast cancer with a previously constructed chimeric VEGF vaccine from shuffling. RESULTS: Combined vaccination with chimeric EGF and VEGF from shuffling could induce high titer of antibodies against EGF and VEGF to inhibit tumor growth and angiogenesis, and improve the survival rate of mice with breast cancer...
May 16, 2017: Immunotherapy
https://www.readbyqxmd.com/read/28504251/programmable-co-delivery-of-the-immune-checkpoint-inhibitor-nlg919-and-chemotherapeutic-doxorubicin-via-a-redox-responsive-immunostimulatory-polymeric-prodrug-carrier
#8
Jing-Jing Sun, Yi-Chao Chen, Yi-Xian Huang, Wen-Chen Zhao, Yan-Hua Liu, Raman Venkataramanan, Bin-Feng Lu, Song Li
To achieve synergistic therapeutic efficacy and prevent cancer relapse, chemotherapy and immunotherapy have been combined as a new modality for tumor treatment. In this work, we designed a redox-responsive immunostimulatory polymeric prodrug carrier, PSSN10, for programmable co-delivery of an immune checkpoint inhibitor NLG919 (NLG) and a chemotherapeutic doxorubicin (DOX). NLG-containing PSSN10 prodrug polymers were self-assembled into nano-sized micelles that served as a carrier to load DOX (DOX/PSSN10 micelles)...
May 8, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28501600/development-of-a-human-epidermal-growth-factor-derivative-with-egfr-blocking-and-depleted-biological-activities-a-comparative-in-vitro-study-using-egfr-positive-breast-cancer-cells
#9
Masomeh Mehrabi, Kamran Mansouri, Bijan Soleymani, Zohreh Hoseinkhani, Mohsen Shahlaie, Reza Khodarahmi
Epidermal growth factor (EGF) is a local growth factor that stimulates cell growth, proliferation, and differentiation by binding to its receptor EGFR. EGF and EGFR are involved in many aspects of the development of carcinomas. Because EGFR has been found to be over-expressed in many tumors of epithelial origin, it is a potential target for antitumor therapy. In this study we designed a mutated form of hEGF (mEGF) with a deletion of four amino acids residues (Gln(43), Tyr(44), Arg(45) and Asp(46)) in order to show importance of Leu spatial location for EGFR binding/activation...
May 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28491135/highlights-from-the-15th-st-gallen-international-breast-cancer-conference-15-18-march-2017-vienna-tailored-treatments-for-patients-with-early-breast-cancer
#10
Consuelo Morigi
The 15th St Gallen International Breast Cancer Conference was held in Vienna for the second time, from 15th-18th March 2017. 4000 people from 105 countries all over the world were invited to take part in the event. The real highlight of the conference was the last day with the International Consensus Session which was chaired by around 50 experts on breast cancer worldwide. With reference to data from scientific research, the consensus panel tried to offer guidelines for the management of breast cancer with the aim of providing patients with optimal treatment...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28489980/practical-approach-to-triple-negative-breast-cancer
#11
Vijayakrishna K Gadi, Nancy E Davidson
Triple negative is a term applied to breast cancers that do not meaningfully express the estrogen or progesterone hormone receptors or overexpress the human epidermal growth factor receptor 2 tyrosine kinase. At present, the only proven method for systemic management of triple-negative breast cancer for both early-stage and metastatic settings is cytotoxic chemotherapy. Here, we provide a comprehensive review of management strategies that are best supported by available data. We also review recent advances most likely to affect treatment of triple-negative breast cancer in the coming years with particular emphasis on targeted agents, biologics, and immunotherapy...
May 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28488143/methodology-of-phase-ii-clinical-trials-in-metastatic-elderly-breast-cancer-a-literature-review
#12
REVIEW
B Cabarrou, L Mourey, F Dalenc, L Balardy, D Kanoun, H Roché, J M Boher, M E Rougé-Bugat, Thomas Filleron
PURPOSE: As the incidence of invasive breast cancer will increase with age, the number of elderly patients with a diagnosis metastatic breast cancer will also rise. But the use of cytotoxic drugs in elderly metastatic breast cancer patients is not systematic and is dreaded by medical oncologists. The need for prospective oncologic data from this population seems increasingly obvious. The main objective of this review is to investigate design and characteristics of phase II trials that assess activity and feasibility of chemotherapies in elderly advanced/metastatic breast cancer patients...
May 9, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28488141/elevated-t-cell-activation-score-is-associated-with-improved-survival-of-breast-cancer
#13
Lingeng Lu, Yalai Bai, Zuoheng Wang
PURPOSE: Immune checkpoints cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death 1 receptor (PD-1) negatively regulate CD8(+) T cell functions, impeding the capacity of effector T cells to kill tumors. Here, we study the prognostic significance of CTLA4, PD-1 and T cell activation status in breast cancer. METHODS: Using a publicly accessed RNA-seq dataset including 1087 breast cancer patients, we performed Kaplan-Meier survival curves and multivariate Cox regression models to evaluate the associations of CTLA4, PD-1, and weighted T cell activation score with patients' overall survival...
May 9, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28487507/transcriptional-regulation-of-foxp3-requires-integrated-activation-of-both-promoter-and-cns-regions-in-tumor-induced-cd8-treg-cells
#14
Sreeparna Chakraborty, Abir K Panda, Sayantan Bose, Dia Roy, Kirti Kajal, Deblina Guha, Gaurisankar Sa
T-regulatory cells are an upsurge in the tumor microenvironment and induce immune-evasion. CD4(+) Treg cells are well characterized whereas the role of CD8(+) Tregs in cancer has recently started to crease attention. Here, we report an augmentation CD8(+)FOXP3(+) Tregs in breast tumor microenvironment. FOXP3, the lineage-specific transcription factor, is a dominant regulator of Treg cell development and function. FOXP3 is induced preferentially by divergent signaling in CD4(+) Treg cells. But how FOXP3 is induced and maintained in tumor-CD8(+) Tregs is the Cinderella of the investigation...
May 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28486273/zebularine-treatment-induces-mage-a11-expression-and-improves-ctl-cytotoxicity-using-a-novel-identified-hla-a2-restricted-mage-a11-peptide
#15
Jiandong Zhang, Meixiang Sang, Lina Gu, Fei Liu, Weijing Li, Danjing Yin, Yunyan Wu, Shina Liu, Weina Huang, Baoen Shan
Melanoma-associated antigen-A11 (MAGE-A11) is frequently expressed in breast cancer and is associated with poor prognosis. Therefore, MAGE-A11 is a potential immunotherapy target in breast cancer. MAGE-A11 expression, however, is downregulated in many patients, thus constraining the application of immunotherapy. The induction of MAGE-A11 expression is crucial for the recognition and killing of breast cancer cells by cytotoxic T lymphocytes (CTL). In this study, a series of HLA-A2-restricted candidate MAGE-A11 peptides were predicted, synthesized, and tested...
May 8, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28474709/-main-immunoregulatory-mechanisms-that-favor-breast-cancer-development
#16
Gina Stella García-Romo, Karen Guadalupe García-Castillo, Álvaro Díaz-Rodríguez, Diana Reyes-Hernández, Alexander Pedroza-González
Even after the improvements made in recent years in early diagnosis and treatments, breast cancer is still the most common cancer and the leading cause of cancer death in women around the world. Several attempts to design new alternative therapies like immunotherapy have been evaluated in clinical trials, but they have shown limited efficacy. The failure of immunotherapy may be related to suppressive mechanisms in the tumor environment. Consequently, the development of new immunotherapy based treatment strategies is very important to understand the immunoregulatory mechanisms present in the tumor microenvironment...
March 2017: Gaceta Médica de México
https://www.readbyqxmd.com/read/28473315/4-1bb-enhanced-expansion-of-cd8-til-from-triple-negative-breast-cancer-unveils-mutation-specific-cd8-t-cells
#17
Michiko Harao, Marie-Andrée Forget, Jason Roszik, Hui Gao, Gildy V Babiera, Savitri Krishnamurthy, Jessica A Chacon, Shumin Li, Elizabeth A Mittendorf, Sarah M DeSnyder, Korrene F Rockwood, Chantale Bernatchez, Naoto T Ueno, Laszlo G Radvanyi, Luis Vence, Cara Haymaker, James M Reuben
Triple negative breast cancer (TNBC) highly infiltrated with CD8(+) tumor-infiltrating lymphocytes (TILs) has been associated with improved prognosis. This observation led us to hypothesize that CD8(+) TIL could be utilized in autologous adoptive cell therapy for TNBC, although this concept has proven to be challenging, given the difficulty in expanding CD8(+) TILs in solid cancers other than melanoma. To overcome this obstacle, we used an agonistic antibody  (urelumab) to a TNFR family member, 4-1BB/CD137, which is expressed by recently activated CD8(+) T cells...
May 4, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28468826/neuropilin-1-mediates-neutrophil-elastase-uptake-and-cross-presentation-in-breast-cancer-cells
#18
Celine Kerros, Satyendra C Tripathi, Dongxing Zha, Jennifer M Mehrens, Anna Sergeeva, Anne V Philips, Na Qiao, Haley L Peters, Hiroyuki Katayama, Pariya Sukhumalchandra, Kathryn E Ruisaard, Alexander A Perakis, Lisa S St John, Sijie Lu, Elizabeth A Mittendorf, Karen Clise-Dwyer, Amanda C Herrmann, Gheath Alatrash, Carlo Toniatti, Samir M Hanash, Qing Ma, Jeffrey J Molldrem
Neutrophil elastase (NE) can be rapidly taken up by tumor cells that lack endogenous NE expression, including breast cancer, which results in cross-presentation of PR1, an NE-derived HLA-A2-restricted peptide that is an immunotherapy target in hematological and solid tumor malignancies. The mechanism of NE uptake, however, remains unknown. Using the mass spectometry-based approach, we identify neuropilin-1 (NRP1) as a NE receptor that mediates uptake and PR1 cross-presentation in breast cancer cells. We demonstrated that soluble NE is a specific, high-affinity ligand for NRP1 with a calculated Kd=38...
May 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28459460/magea1-interacts-with-fbxw7-and-regulates-ubiquitin-ligase-mediated-turnover-of-nicd1-in-breast-and-ovarian-cancer-cells
#19
J Zhao, Y Wang, C Mu, Y Xu, J Sang
Melanoma-associated antigen A1 (MAGEA1) is member of the MAGE gene family that is expressed in male germ line cells and placenta under normal physiological conditions. Although MAGEA1's expression levels have been evaluated as one of the cancer testis (CT) antigens for immunotherapy in melanoma and several other cancers, its functional role and signaling mechanisms are largely unknown. In this study, we examined the functional involvement and signaling mechanisms of MAGEA1 in breast and ovarian cancer cells...
May 1, 2017: Oncogene
https://www.readbyqxmd.com/read/28455976/myeloid-derived-suppressor-cell-and-macrophage-exert-distinct-angiogenic-and-immunosuppressive-effects-in-breast-cancer
#20
Zhaoxu Fang, Chengwen Wen, Xiaolan Chen, Rongping Yin, Chenglin Zhang, Xiaohua Wang, Yuhui Huang
The immunosuppressive tumor microenvironment is a key obstacle to hinder a cancer immunotherapy. Myeloid-derived suppressor cells (MDSCs) have been considered as a major player in immunosuppression. In this study, we find that tumor-infiltrating MDSCs (tiMDSCs) are less immunosuppressive than tumor-associated macrophages (TAMs) in multiple murine orthotopic breast tumor models. Compared to TAMs, tiMDSCs produce higher levels of pro-inflammatory factors and lower levels of anti-inflammatory factors. Furthermore, tiMDSCs are preferentially located in hypoxic areas and are more pro-angiogenic than TAMs...
April 10, 2017: Oncotarget
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